Recognition and removal by phagocytes is the culmination of the death process for most apoptotic cells. Loss of phospholipid asymmetry leads to exposure of phosphatidylserine (PS) on the apoptotic cell surface; the polar head group of this phospholipid is recognized in a stereospecific manner, suggesting the existence of a PS-specific receptor. Using phage display and biopanning, we have cloned a novel gene we believe to be an authentic PS receptor; the mammalian protein has homologues in Drosophila and in C. elegans, the function of which are unknown. The protein is expressed on the surface of macrophages, fibroblasts, and epithelial cells, all of which can engulf apoptotic cells. Monoclonal antibodies against this receptor inhibit uptake of apoptotic cells only by those phagocytes which are inhibited by PS liposomes. Furthermore, binding of the antibodies to the cell surface is inhibited by PS, but not by other anionic phospholipids. Transfection of the gene into Jurkat cells, which do not express the gene normally, induced the ability to bind to and take up apoptotic cells: this was not seen in Jurkats transfected with empty vector. Using biochemical, molecular, and genetic methods (including RNAi and transformation rescue in C. elegans), the investigators hope to define the function of this receptor and its ligand specificity. The investigators hypothesize that PS recognition has been preserved throughout phylogeny as an effective mechanism mediating the removal of apoantibodies.